Most of the clinically used anti-cancer drugs, such as paclitaxel, docetaxel, doxorubicin, have poor water solubility. Often these drugs cannot be directly administered, e.g., parenterally, to patients. For example, paclitaxel and many of its derivatives and analogues have exceedingly low solubility in most physiologically acceptable aqueous solvents that would be compatible with intravascular administration. Thus, a surfactant as an excipient is often necessary to facilitate in vivo delivery of the effective compound. For example, Taxotere® (Sanofi-Aventis) is a formulation of docetaxel with polysorbate 80 as the excipient, along with ethanol and citric acid. The paclitaxel formulation Taxol® (Bristol-Myers Squibb) is formulated using Cremophor® EL, a polyoxyethylated castor oil. This formulation contains 50% (v/v) alcohol, as well as an 88-fold excess of Cremophor® EL, which has a potential for inducing serious side effects. The acute and common clinical side effects of the paclitaxel formulation are severe: listing dyspnea, hypotension, angioedema, generalized urticaria, and most notably anaphylactoid reactions, with risk for a fatal outcome. In addition, the high Cremophor® EL concentrations facilitate the leaking of “plasticizers,” i.e., chemicals used in the manufacture of disposable infusion bags and tubing sets into the infusate. The long-term risks of patient exposure to these chemicals are unknown. Thus, the excipients in these drug formulations may lead to serious side effects, such as allergy, renal toxicity, nerve and heart toxicity, and in certain cases, has mandated premedication with diphenhydramine, H2-antagonists, and even corticosteroids.
Accordingly, there is need for alternative drug compositions and formulations of anti-cancer drugs, in order to alleviate dangerous side effects and provide a more even drug supply for both conventional dose therapy and for high dose chemotherapy. The present disclosure addresses the need.